How the brain is organized into the neuronal circuits that carry out the processing of visual information has long been in question. In the brain of Drosophila, photoreceptor cell axons and the cortical axons of the optic ganglia form precise topographic interconnections. We are using a genetic approach to identifying the molecules involved in the establishment of this connective architecture. A genetic screen for defects in the establishment of neuronal connectivity in the visual system resulted in the recovery of mutations at fifty-seven loci. Included in this collection are mutations that affect the signaling mechanisms underlying the assignment of cell fate in the visual primordia, and interactions between axons and prospective target cells during the establishment of connectivity. We will: 1) study the function of a Drosophila member of the Cytohesin family in controlling the response of neuronal precursor cells to retinal axon-borne differentiation signals, 2) conduct a small-scale screen for loci involved in the generation of axonal connectivity based on protein localization reported by a GFP gene-trap transposon, 3) perform a screen for mutations that disrupt the local fine structure of lamina synaptic circuitry and characterize some of the loci identified, 4) isolate mutations at the eph and ephrin loci, and examine their consequences for nervous system development. Given the conservation between the mechanisms that pattern the nervous systems of vertebrates and invertebrates, these studies will likely yield important insights into the development of the complex architectures of the brains of vertebrates, including humans.